Gryazov A. Radiosurgical treatment with diagnostic support for glioblastoma, taking into account the molecular genetic structure of the tumor

The dissertation presents the results of radiosurgical treatment of glioblastoma, during which a number of scientific problems were solved, which made it possible to increase the effectiveness of treatment taking into account the molecular features of the most malignant brain tumor - glioblastoma, through the use of radiosensitization during stereotaxic radiosurgery, the use of preoperative radiosurgery, the development of criteria for its prognosis efficiency and scientific justification of the algorithm of diagnostic support of patients. In order to solve the problems of scientific work in the period from 2014 to 2021 in the department of radioneurosurgery of the State University "Institute of Neurosurgery named after Acad. A.P. Romodanova of the National Academy of Medical Sciences of Ukraine" 166 patients with glioblastoma (WHO Grade IV) were examined and treated by the method of stereotaxic radiosurgery (WHO Grade IV). Patients were divided into three cohorts. I. 106 patients who underwent radiosurgery with radiosensitization with nitroimidazoles (metronidazole and nimorazole) - 66 patients - the main group, and 40 - the control group, in which SRH was performed without radiosensitization. II. 38 patients with recurrent multifocal glioblastoma who underwent radiosurgery with oxygen radiosensitization. III. 22 people underwent preoperative radiosurgery. All patients underwent treatment on the linear accelerator "Linac" of the BrainLab company using the method of radiosurgical irradiation. When conducting radiosurgical treatment of primary glioblastomas, we took into account the data of the molecular genetic structure of the tumor. 9 Stereotaxic radiosurgery was performed for one or more fractions (3-5 fractions) in 166 patients (average age of patients 55 years, interval 28-82), 96 men (57.83%), and 70 women (42.16%). With single-fraction SRH, the average dose was 18.4 Gy. With SRH in 5 fractions, the average dose per fraction was 6.55 Gy, the total dose was 32.7 Gy (interval 25-40 Gy). The average volume of irradiated tumors was 29.21 cm3 , 66 patients had primary glioblastomas, 40 patients had recurrent ones. 38 patients had multifocal recurrent glioblastoma in whom radiosensitization was performed with oxygen. Before the radiosurgery session, patients must have their SpO2 blood oxygenation (number of liters per minute of O2) tested, if necessary raising the O2 content to 100%. 2 hours before CPR, patients took orally 2 g of metronidazole (MTN, M+), or 2 g of nimorazole (HMP, H+), or oxygen infusion was performed ("oxygen test" (CPR+O2). During the radiosurgery session, oxygen infusion was carried out under the control of a pressure, pulse and oxygen level sensor in the patient's blood. MRI with standard protocols, as well as diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI), with ADC diffusion coefficient acquisition and BOLD program, were performed before oxygen perfusion, 20 minutes after oxygen perfusion, and then again after the radiosurgery session (in 40 minutes). The duration of the oxygen perfusion session was 20 minutes, followed by a radiosurgery session. We determined that the hypoxic zone of the outer circle of glioblastoma is detected only in the BOLD program and only after the "oxygen test" before and after the introduction of 95% oxygen using an oxygenator. The most sensitive prognostic test for the effectiveness of CPR is MRI DWI with the definition of the diffusion coefficient in the area of intermediate hypoxia (sensitivity - 94.0%, specificity - 83.1%), while the highest specificity indicators (86.0) are demonstrated by the BOLD program, the least sensitive (82.0%) and specific (68.2%) indicators of early volumetric tumor regression. On the basis of the obtained data, with a reliable significance of 0.0000, it was confirmed that an increase in the ADC index and a decrease in the BOLD index are predictors of early response to radiosurgical treatment of glioblastoma.